Usher Syndrome (USH) is the most frequent cause of hereditary deaf-blindness in humans. Depending on the severity of clinical symptoms, USH can be divided into three clinical subtypes, with USH1 the most severe form of the disease. The gene products of nine USH disease genes have been identified so far, including five USH1 genes and three USH2 genes, which are highly conserved from flies to humans. In this study, I will focus on the embryonic salivary glands and trachea of Drosophila melanogaster because they are relatively simple tubular organs highly amenable to genetic and cellular analyses and all five of the Drosophila homologues to the USH1 genes are strongly expressed in these tissues. My preliminary studies revealed that loss and/or gain-of-function mutations in the three USH1 fly homologues including ck, Cad99C and sans that I have so far examined result in defects in salivary gland morphogenesis. I will determine the role of USH genes in tubular organ morphogenesis and characterize the interaction between the USH genes and other known genes affecting apical membrane dynamics. The long-term goal of my proposed study is to learn how the USH genes function in morphogenesis of the Drosophila salivary gland and trachea. By learning how the USH genes function at the cellular and molecular level during the formation of the relatively simple Drosophila salivary gland and trachea, I expect to gain important insight into how the USH genes function in human development and disease. PUBLIC HEALTH RELEVANCE: In the proposed studies, I will characterize the Usher Syndrome (USH) genes in Drosophila tube system. USH is the most common form of deaf-blindness in humans. By characterizing USH genes in the relatively simple, but genetically amenable organs, I expect to reveal some key aspects of USH and such knowledge can then be used to address the disease.